Decoding the endometrial niche of Asherman’s Syndrome at single-cell resolution

Infertility; Molecular medicineInfertilidad; Medicina molecularInfertilitat; Medicina molecularAsherman’s Syndrome is characterized by intrauterine adhesions or scarring, which cause infertility, menstrual abnormalities, and recurrent pregnancy loss. The pathophysiology of this syndrome remains unknown, with treatment restricted to recurrent surgical removal of intrauterine scarring, which has limited success. Here, we decode the Asherman’s Syndrome endometrial cell niche by analyzing data from over 200,000 cells with single-cell RNA-sequencing in patients with this condition and through in vitro analyses of Asherman’s Syndrome patient-derived endometrial organoids. Our endometrial atlas highlights the loss of the endometrial epithelium, alterations to epithelial differentiation signaling pathways such as Wnt and Notch, and the appearance of characteristic epithelium expressing secretory leukocyte protease inhibitor during the window of implantation. We describe syndrome-associated alterations in cell-to-cell communication and gene expression profiles that support a dysfunctional pro-fibrotic, pro-inflammatory, and anti-angiogenic environment.This study was jointly supported by Human Uterus Cell Atlas Project from the European Union’s Horizon 2020 research and innovation program under grant agreement No. 874867, PROMETEO/2018/161 from the Valencia Government, IDI-20201142 CDTI from the Spanish Government and Carlos Simon Foundation, Spain. X.S. and E.F. were partially supported by IDI-20201142 CDTI from the Spanish Government. B.R. was supported by the H2020-funded project Human Uterus Cell Atlas (HUTER) (2020/2021) (Grant Agreement 874867). R.P. was supported by an Industrial Doctorate grant (DIN2020-011069) from the Spanish Ministry of Science and Innovation (MICINN). N.V. was supported by PROMETEO/2018/161. J.G.F. was supported by a PFIS grant [FI19/00159]. J.L. was supported by INVEST/2022/478 program. A.S. was supported by Estonian Research Council (PRG1076) and Horizon 2020 innovation grant (ERIN, grant no. EU952516). I.M. was supported by an FIS project grant [PI21/00235]. F.V. was supported by an FIS project grant [PI21/00528]. Other data that support the findings of this study are available from Asherman Therapy SL. Restrictions apply to data access with data used under license for the current clinical study and are not publicly available. Data are, however, available from the authors upon reasonable request and with permission of the Vall Hebron Ethical Committee

Data from: Insights into the human mesenchymal stromal/stem cell identity through integrative transcriptomic profiling

Background: Mesenchymal Stromal/Stem Cells (MSCs), isolated under the criteria established by the ISCT, still have a poorly characterized phenotype that is difficult to distinguish from similar cell populations. Although the field of transcriptomics and functional genomics has quickly grown in the last decade, a deep comparative analysis of human MSCs expression profiles in a meaningful cellular context has not been yet performed. There is also a need to find a well-defined MSCs gene-signature because many recent biomedical studies show that key cellular interaction processes (i.e. inmuno-modulation, cellular cross-talk, cellular maintenance, differentiation, epithelial-mesenchymal transition) are dependent on the mesenchymal stem cells within the stromal niche. Results: In this work we define a core mesenchymal lineage signature of 489 genes based on a deep comparative analysis of multiple transcriptomic expression data series that comprise: (i) MSCs of different tissue origins; (ii) MSCs in different states of commitment; (iii) other related non-mesenchymal human cell types. The work integrates several public datasets, as well as de-novo produced microarray and RNA-Seq datasets. The results present tissue-specific signatures for adipose tissue, chorionic placenta, and bone marrow MSCs, as well as for dermal fibroblasts; providing a better definition of the relationship between fibroblasts and MSCs. Finally, novel CD marker patterns and cytokine-receptor profiles are unravelled, especially for BM-MSCs; with MCAM (CD146) revealed as a prevalent marker in this subtype of MSCs. Conclusions: The improved biomolecular characterization and the released genome-wide expression signatures of human MSCs provide a comprehensive new resource that can drive further functional studies and redesigned cell therapy applications

Data from: Insights into the human mesenchymal stromal/stem cell identity through integrative transcriptomic profiling

Background: Mesenchymal Stromal/Stem Cells (MSCs), isolated under the criteria established by the ISCT, still have a poorly characterized phenotype that is difficult to distinguish from similar cell populations. Although the field of transcriptomics and functional genomics has quickly grown in the last decade, a deep comparative analysis of human MSCs expression profiles in a meaningful cellular context has not been yet performed. There is also a need to find a well-defined MSCs gene-signature because many recent biomedical studies show that key cellular interaction processes (i.e. inmuno-modulation, cellular cross-talk, cellular maintenance, differentiation, epithelial-mesenchymal transition) are dependent on the mesenchymal stem cells within the stromal niche. Results: In this work we define a core mesenchymal lineage signature of 489 genes based on a deep comparative analysis of multiple transcriptomic expression data series that comprise: (i) MSCs of different tissue origins; (ii) MSCs in different states of commitment; (iii) other related non-mesenchymal human cell types. The work integrates several public datasets, as well as de-novo produced microarray and RNA-Seq datasets. The results present tissue-specific signatures for adipose tissue, chorionic placenta, and bone marrow MSCs, as well as for dermal fibroblasts; providing a better definition of the relationship between fibroblasts and MSCs. Finally, novel CD marker patterns and cytokine-receptor profiles are unravelled, especially for BM-MSCs; with MCAM (CD146) revealed as a prevalent marker in this subtype of MSCs. Conclusions: The improved biomolecular characterization and the released genome-wide expression signatures of human MSCs provide a comprehensive new resource that can drive further functional studies and redesigned cell therapy applications

Future pharmacists' use of, and attitudes towards, cognitive enhancers

KEGGmap “hsa04060: Cytokine-cytokine receptor interaction”. Red-colour boxes are differentially over-expressed genes in HPCs with respect to MSCs. Yellow coloured genes are over-expressed in MSCs relative to HPCs. (PNG 63 kb

GeneConservation

Text file of sequences aligned for gene conservation calculations. Conservation scores from alignments of 100 vertebrate species (known as UCSC hg19phastCons) were annotated with the phastCons100way.UCSC.hg19 package (R/Bioconductor)

Low resolution ultra-violet spectra of symbiotic stars. Developments over thirteen years

Consideration is made of 651 low resolution ultra-violet spectra of 19 symbiotic stars obtained from the archives of the 1TIE Space Observatory. A classification is made of these stars by considering the stability of the ratio of flux intensities of selected high energy emission lines from them. Unexpected chronological con-elation of the behaviour of these ratios is noted with respect to two symbiotic stars, it is believed that this correlation has not previously been reporte